Multiscale rational construction strategy for polyphenol self-assembled delivery systems: from nanoscale to microscale

Natural polyphenols have garnered significant attention in pharmaceuticals, food, and cosmetics due to their unique bioactive functions such as antioxidant, anti-inflammatory, antitumor, and antibacterial properties. The multiple phenolic hydroxyl groups in polyphenol molecules (catechol and galloyl moieties) enable dynamic complexation with various substances through non-covalent interactions, including hydrogen bonding, hydrophobic interactions, electrostatic interactions and coordination bonding. The excellent self-assembly and interfacial properties of polyphenols enable the construction of multiscale and multifunctional delivery systems, ranging from nanoscale to microscale. Microscale delivery systems play an irreplaceable role in disease treatment, and research on polyphenol-based microscale delivery systems is gaining momentum. This review systematically describes various polyphenol-based microscale delivery systems, including coacervate droplets, Pickering emulsions, microcapsules, microparticles, and polyphenol-modified microbes and cells, and discusses their self-assembly mechanisms, preparation methods, functional characteristics and therapeutic applications. Finally, we outline the research advances in polyphenol self-assembled delivery systems and discuss future directions for the development of next-generation polyphenol-based biomaterials.